Protection by WR-2721 of human bone marrow function following irradiation.

Protection by WR-2721 of bone marrow (BM) from depression following hemibody irradiation (HBI) was assessed in patients receiving palliative therapy for widespread symptomatic metastasis on a Phase I/II Radiation Therapy Oncology Group (RTOG) protocol. Twenty-five patients are currently evaluable for the assessment of hematologic toxicity. HBI (600 or 700 cGy) was delivered starting 15-30 min after WR-2721 (600-900 mg/m2) intravenous infusion. Twenty patients from previous RTOG HBI studies were comparable in terms of radiation dose, hematologic data, and previous cytotoxic therapy. The WBC and platelet count nadirs at any time within 6 wk following HBI were used for data analysis, and toxicity was rated according to RTOG criteria. For the patients treated with WR-2721, moderate, severe, or life-threatening toxicity were seen in 16%, 12%, and 0% of the patients, respectively, compared to 30%, 15%, and 10% of patients in the group not treated with WR-2721. For the subpopulation of patients treated with the higher irradiation dose (700 cGy), differences in toxicity appeared to be greater. Conversely, for the sub-population of patients treated only to the upper hemibody, the difference in toxicity was less apparent. The percentage change from the median pre-treatment white blood cell (WBC) and platelet counts (PC) was not different between the WR-2721 treated and non-treated group; however, the median WBC count for the WR-2721 group returned to the pre-treatment value by the fourth week following HBI, whereas, it remained at 61% of the pre-HBI value for the control group. Within the group of patients treated with WR-2721, 5 of 17 (29%) receiving 600 mg/m2 demonstrated a greater than 75% decline in either WBC or platelets, compared to 0/8 patients treated with 750-900 mg/m2. These preliminary data support a protective effect by WR-2721 on radiation-induced bone marrow depression in humans, which may become more apparent with the use of higher radiation and WR-2721 doses.